Plasmodium Falciparum InfectionPhase 3AL3vs5NCT02020330
Optimising Operational Use of Artemether-lumefantrine Comparing 3 Day Versus 5 Day
A Phase 3 study testing Artemether-lumefantrine 3 days and Artemether-lumefantrine 5 days in people with Plasmodium Falciparum Infection, run by University of Oxford at 1 site in Burma.
Trial summary
This is a randomised two arm study, comparing artemether-lumefantrine 3 days and 5 days treatment. Patients will be randomised in blocks of ten to one of the two treatment arms. The standard regimen is twice daily for three days with a delay of at least eight hours between the first and second doses. Read more about this study
- Who is it for?
- Ages 6 years and older
- Conditions the study is for
- Plasmodium Falciparum Infection
- What is being tested?
- Artemether-lumefantrine 3 days and Artemether-lumefantrine 5 days
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteBurma
- Study dates
- 25 Nov 2013to 25 Mar 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥ 6 year
- Symptomatic malaria infection, i.e. history of fever or presence of fever >37.5°C
- Microscopic confirmation of asexual stages of P. falciparum (may be mixed with non-falciparum species) with parasitaemia PFT≥5/500 WBC
- Written informed consent given to participate in the trial
Who cannot join
- Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age unless menstruating).
- Female of 12 to 18 years of age
- P. falciparum asexual stage parasitaemia greater than or equal to 4% red blood cells (175,000/µL).
- Signs or symptoms indicative of severe malaria including:
- Impaired consciousness (Blantyre Coma Score <5 or Glasgow Coma Scale <15)
- Severe anaemia (Hb% <5 mg/dl)
Show all 13Show fewer
- Bleeding disorder -evidenced by epistaxis, bleeding gums, frank haematuria, bleeding from venepuncture sites
- Respiratory distress
- Severe jaundice
- Haemodynamic shock
- A full course of artemether-lumefantrine treatment in the previous 28 days
- Known hypersensitivity to artemisinins - defined as history of erythroderma/other severe cutaneous reaction, angioedema or anaphylaxis
- History of splenectomy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label Randomized Controlled Trial to Evaluate the Effectiveness and Safety of a 3 Day Versus 5 Day Course of Artemether-lumefantrine for the Treatment of Uncomplicated Falciparum Malaria in Myanmar
This is a randomised two arm study, comparing artemether-lumefantrine 3 days and 5 days treatment. Patients will be randomised in blocks of ten to one of the two treatment arms. The standard regimen is twice daily for three days with a delay of at least eight hours between the first and second doses. A single of primaquine will be given to all patients on the first day of treatment for gametocytocidal activity. The initial treatment will be given under supervision, all other subsequent doses will be given to the patient to the taken at home. Patients will be followed up for nine visits over forty two days.
Read the detailed description
- The study will be conducted in 6 village health centres in the Mon and Kayin states
- The patient or parent/guardian (in case of minor or under aged) must personally sign and date the latest approved version of the informed consent form before any study specific procedures are performed
- A case record form will be completed for each patient documenting symptoms prior to clinic attendance, concomitant illness, drug history. Height, weight, vital signs and physical examination findings will be recorded.
- At enrolment (D0) all patients will have the following samples taken:
- Repeat parasite count (thick and thin films). Treatment should be started without waiting for the result.
- Filter paper blood blots (3 dots on Whatman 3MM filter paper approx 180-300 µL blood) for parasite genotyping (MSP1, MSP2, GLURP in case of recurrence during follow-up)
- Haemoglobin
- Laboratory procedures
- Slide microscopy: Thick and thin blood films stained with Giemsa will be read and counts expressed as the number of parasites per 500 white blood cells
- Molecular studies: The samples will be used to detect asexual parasites (blood smear, sensitive PCR), parasite population structure (Sequenom genotyping and sequencing), gametocytes (microscopy). The samples will be stored in a cool box and kept maximum 5 days in the field and will be transported to the local laboratory for processing. Plasma and buffy coat will be separated, frozen and stored. The frozen packed red cells will be transported to the molecular laboratory at MORU, Bangkok, Thailand, for sample processing (DNA extraction, quantitative PCRs).
- Conditions
- Plasmodium Falciparum Infection
- Being tested
- Artemether-lumefantrine 3 days, Artemether-lumefantrine 5 days
- Keywords
- falciparum, malaria
- Medical subject headings
- Malaria, Falciparum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Artemether-lumefantrine 3 daysDrug
Also called Coartem®, Novatis, Switzerland
One tablet contains 20mg artemether and 120mg lumefantrine. The standard regimen is twice daily for 3 days with a delay of at least 8 hours between the first and second dose. It is dosed by weight categories. One gram of fish oil will be given to half of the participants in the 3 days arm.
Artemether-lumefantrine 5 daysDrug
Also called Coartem®, Novartis, Switzerland
One tablet contains 20mg artemether and 120mg lumefantrine. The experiment regimen is twice daily for 5 days with a delay of at least 8 hours between the first and second dose. It is dosed by weight categories. One gram of fish oil will be given to half of the participants in the 5 days arm.
| Study group | Role | What they receive |
|---|---|---|
| AL3days | Active comparator | Artemether-lumefantrine 3 days Receives: Drug: Artemether-lumefantrine 3 days |
| AL5days | Experimental | Artemether-lumefantrine 5 days Receives: Drug: Artemether-lumefantrine 5 days |
What is being measured
The primary outcome is the main question the study is designed to answer.
proportion of patients with detectable parasitaemia
Assessed by sensitive PCR on days 5 and 7 after treatment
Measured: On day 5 and day 7
Secondary outcomes (8)
Parasitaemia clearance time
Assessed by sensitive PCR on D3 in the 3 day arm and D5 in the 5 day arm
Measured: On day 3 and Day 5
Gametocyte carriage rates
Measured: Day 7
artemether-lumefantrine tolerability
Tolerability of artemether-lumefantrine will be assessed by comparing the proportion of patients with anorexia, nausea, vomiting, abdominal pain and other symptoms of administration between the intervention arm and the control arm
Measured: 5 days
Comparison of effectiveness
Comparison of effectiveness uncorrected and corrected will be assessed by PCR genotyping
Measured: Day 42
concentrations of lumefantrine
Measured: Day 7
Haematological recovery rate
Assessed by comparing hemoglobin between baseline and after treatment at day 28
Measured: Day 28
Incidence of vivax malaria relapses
Assessed by the microscopist find malaria smear positive within the follow up period
Measured: 42 days
Comparison of addition of food supplement (fish oil)
Assessed by comparing lumefantrine concentration on day 7 and proportion of patients with detectable parasitaemia by qPCR
Measured: day 3 to day 21
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2013 (estimated)
- Study start25 Nov 2013
- Primary completion4 Feb 2015
- Study completion25 Mar 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Plasmodium Falciparum InfectionStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Frank Smithuis, MD, Principal investigator, Myanmar Oxford Clinical Research Unit
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02020330
- Sponsor's protocol ID
- MOCRU1301
- Acronym
- AL3vs5
- Status last verified
- Sep 2018
- First submitted
- 30 Oct 2013
- Last updated
- 20 Sep 2018
- Results posted
- No
- Data monitoring committee
- No
Publications
Tun KM, Jeeyapant A, Myint AH, Kyaw ZT, Dhorda M, Mukaka M, Cheah PY, Imwong M, Hlaing T, Kyaw TH, Ashley EA, Dondorp A, White NJ, Day NPJ, Smithuis F. Effectiveness and safety of 3 and 5 day courses of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in an area of emerging artemisinin resistance in Myanmar. Malar J. 2018 Jul 11;17(1):258. doi: 10.1186/s12936-018-2404-4.
PubMed 29996844
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label Randomized Controlled Trial to Evaluate the Effectiveness and Safety of a 3 Day Versus 5 Day Course of Artemether-lumefantrine for the Treatment of Uncomplicated Falciparum Malaria in Myanmar
- ClinicalTrials.gov ID
- NCT02020330
- Acronym / sponsor ID
- AL3vs5 / MOCRU1301
- Conditions
- Plasmodium Falciparum Infection
- Keywords
- falciparum, malaria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- 25 Nov 2013 (actual)
- Primary completion
- 4 Feb 2015 (actual)
- Study completion
- 25 Mar 2015 (actual)
- First posted
- 24 Dec 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomised two arm study, comparing artemether-lumefantrine 3 days and 5 days treatment. Patients will be randomised in blocks of ten to one of the two treatment arms. The standard regimen is twice daily for three days with a delay of at least eight hours between the first and second doses. A single of primaquine will be given to all patients on the first day of treatment for gametocytocidal activity. The initial treatment will be given under supervision, all other subsequent doses will be given to the patient to the taken at home. Patients will be followed up for nine visits over forty two days.
Detailed description
- The study will be conducted in 6 village health centres in the Mon and Kayin states
- The patient or parent/guardian (in case of minor or under aged) must personally sign and date the latest approved version of the informed consent form before any study specific procedures are performed
- A case record form will be completed for each patient documenting symptoms prior to clinic attendance, concomitant illness, drug history. Height, weight, vital signs and physical examination findings will be recorded.
- At enrolment (D0) all patients will have the following samples taken:
- Repeat parasite count (thick and thin films). Treatment should be started without waiting for the result.
- Filter paper blood blots (3 dots on Whatman 3MM filter paper approx 180-300 µL blood) for parasite genotyping (MSP1, MSP2, GLURP in case of recurrence during follow-up)
- Haemoglobin
- Laboratory procedures
- Slide microscopy: Thick and thin blood films stained with Giemsa will be read and counts expressed as the number of parasites per 500 white blood cells
- Molecular studies: The samples will be used to detect asexual parasites (blood smear, sensitive PCR), parasite population structure (Sequenom genotyping and sequencing), gametocytes (microscopy). The samples will be stored in a cool box and kept maximum 5 days in the field and will be transported to the local laboratory for processing. Plasma and buffy coat will be separated, frozen and stored. The frozen packed red cells will be transported to the molecular laboratory at MORU, Bangkok, Thailand, for sample processing (DNA extraction, quantitative PCRs).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AL3days | Active comparator | Drug: Artemether-lumefantrine 3 daysArtemether-lumefantrine 3 days |
| AL5days | Experimental | Drug: Artemether-lumefantrine 5 daysArtemether-lumefantrine 5 days |
Who may qualify
- Ages
- 6 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (4 listed)
- Age ≥ 6 year
- Symptomatic malaria infection, i.e. history of fever or presence of fever >37.5°C
- Microscopic confirmation of asexual stages of P. falciparum (may be mixed with non-falciparum species) with parasitaemia PFT≥5/500 WBC
- Written informed consent given to participate in the trial
Key exclusion criteria (13 listed)
- Pregnancy or lactation (urine test for β HCG to be performed on any woman of child bearing age unless menstruating).
- Female of 12 to 18 years of age
- P. falciparum asexual stage parasitaemia greater than or equal to 4% red blood cells (175,000/µL).
- Signs or symptoms indicative of severe malaria including:
- A full course of artemether-lumefantrine treatment in the previous 28 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Artemether-lumefantrine 3 daysAlso: Coartem®, Novatis, SwitzerlandOne tablet contains 20mg artemether and 120mg lumefantrine. The standard regimen is twice daily for 3 days with a delay of at least 8 hours between the first and second dose. It is dosed by weight categories. One gram of fish oil will be given to half of the participants in the 3 days arm. | Drug | AL3days |
| Artemether-lumefantrine 5 daysAlso: Coartem®, Novartis, SwitzerlandOne tablet contains 20mg artemether and 120mg lumefantrine. The experiment regimen is twice daily for 5 days with a delay of at least 8 hours between the first and second dose. It is dosed by weight categories. One gram of fish oil will be given to half of the participants in the 5 days arm. | Drug | AL5days |
Primary outcome
proportion of patients with detectable parasitaemia
Time frame: On day 5 and day 7
Assessed by sensitive PCR on days 5 and 7 after treatment
8 secondary outcomes
Parasitaemia clearance time
Time frame: On day 3 and Day 5
Gametocyte carriage rates
Time frame: Day 7
artemether-lumefantrine tolerability
Time frame: 5 days
Comparison of effectiveness
Time frame: Day 42
concentrations of lumefantrine
Time frame: Day 7
Haematological recovery rate
Time frame: Day 28
Incidence of vivax malaria relapses
Time frame: 42 days
Comparison of addition of food supplement (fish oil)
Time frame: day 3 to day 21
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2018.
- Derived from this study: PubMed 29996844Tun KM, Jeeyapant A, Myint AH, Kyaw ZT, Dhorda M, Mukaka M, Cheah PY, Imwong M, Hlaing T, Kyaw TH, Ashley EA, Dondorp A, White NJ, Day NPJ, Smithuis F. Effectiveness and safety of 3 and 5 day courses of artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in an area of emerging artemisinin resistance in Myanmar. Malar J. 2018 Jul 11;17(1):258. doi: 10.1186/s12936-018-2404-4.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank Smithuis, MD principal investigator
Myanmar Oxford Clinical Research Unit
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Artemether-lumefantrine 3 days and Artemether-lumefantrine 5 days in people with Plasmodium Falciparum Infection, run by University of Oxford at 1 site in Burma.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Burma. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
proportion of patients with detectable parasitaemia (time frame: On day 5 and day 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02020330, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2018.